BIOL 2056 - cell adhesion

types of cell adhesion present in epithelial sheets

1. anchoring junctions

   attach cell to other cells or cells to the ECM

2. tight/occluding junctions

   seal cells together into sheets

3. gap/communicating junctions

   allow exchange of chemical information

epithelial sheets porperties

• anchored to teh basal lamina, therefore are polar

• selectively permeable

• delineate the organs and act as a barrier to leakage —> requires occluding junctions

anchoring junctions

• can transmit mechanical info like stresses

• types of anchoring junctions:

• actin

  • cell-cell junctions called adherance junctions

  • cell-matrix junctions called actin linked cell matrix adhesion

• intermediate filament attachment sites

  • cell-cell junctions called desmosomes

  • cell-matrix junctions called hemidesmosomes

occluding junctions

• seal gaps between epithelia and prevent substance from moving from apical to basal side

• the only way that things can pass through the barriers is through transporters

• also prevents the diffusion of plasma membrane proteins, like transporters, which maintains the polarity of the cell

• E.g the glucose transporter remains on the apical side of the cell, cant move to the basal side

structure of gap junctions

• 6 connexins make a connexon

• homomeric means all the same connexins, whereas heteromeric connexins are diff connexins

• heterotypic is different connexons, whereas homotypic is the same connexon

• the different type of connexin determines the function and permeability

• rapidly assemble and disassemble

signal relaying junctions - E.g chemical synapses

• allow signals to be relayed across the plasma membrane at the site of cell cell contact

• similar in principle to channel forming junctions

• typically include anchorage proteins alongside proteins mediating signal transduction

families of cell adhesion proteins

CADHERINS

• mediate cell-cell attachment

INTEGRINS

• mediate cell-matrix attachments

Ig CAMS

• immunoglobulin superfamily cell adhesion molecules

SELECTINS

• bind carbohydrates

Tight junctions

types of protein present: all homophilic and all part of the CAM superfamily but have features which are specific to tight junctions. Dont individually have roles, only structural roles in maintaining tight junctions

CLAUDINS

• 4 pass transmembrane proteins that constitute the TJ strands

• important for the strength of the TJs

JAMS

• junctional adhesion molecules

• single transmembrane proteins

OCCLUDIN

• 4 pass transmembrane protein localised at TJs

ZO

• important for scaffolding and attaching claudins and occludins to the intracellular cytoskeleton

cadherins

• proteins found in all multicellular animals

• require Ca2+ to mediate cell adhesion

• homophilic - cadherins will only bind to their type

• lots of types can be found within tissues but are separated by spatial segregation

• all cadherins have

  • extracellular domain, intracellular domain, form homodimers

  • the extracellular domain (the N terminus) sticks out and has multiple copies of the cadherin domain which bind to other extracellular N terminuses

  • C terminus is the intracellular domain

• types of cadherin: different in different tissue types and have different structure too E.g: N cadherin in nerve cells, E cadherin in epithelial cells

function and bonding of cadherins

• important for organsiation of tissues, such as the budding of the neural tube and the arrangement of tissue during embryogenesis

  • during neural tube formation, tissue on either side of the budding tube express the same cadherins whilst a section in the middle expressed different cadherins

• H bonding between cadherins is relatively weak

• the sheer no of cadherins make this interaction strong

• multiple cadherin domains are held together by hinge regions

• calcium binding to these hinge regions reduces the flexibility and causes them to reach out

• homophilic interactions - cadherins on one cell type will only bind to the same type of cadherin on the other cell

activation of cadherins via wnt signalling

CADHERIN AND THE CYTOSKELETON

• beta catenin forms a link between the intracellular cadherin domain and the actin cytoskeleton

• the adherans junctions also have the additional related protein p120 catenin

BETA CATENIN AND WNT SIGNALLING

• the ligand (wnt) binds to its receptor called frizzled, this activates dishevelled

• active dishevelled prevents the degradation of beta catenin

• beta catenin, when degraded by dishevelled, is important for replacing the transcriptional repressor groucho, which causes the expression of target genes

• wnt signalling acts as a signalling pathway controlling 1000s of genes, but also occurs in the mediation of adherans juctions

• breakdown of adherans juctions will lead to increased beta catenin —> increased transcription of genes

• however, wnt signalling can also mediate the formation of adherans junctions

integrins structure and binding

STRUCTURE

• have an alpha and beta subunit which bind to peptides in the intracellular domain

• there’s a short intracellular C terminal and a large extracellular N terminal domain

  • the intracellular domain of the beta subunit is important for connecting to the cytoskeleton and mediating signalling

  • the extracellular domain will bind extracellular matrix proteins

BINDING

• heterophilic

• very strongly linked

• needs to be dynamic —> integrins are broken and reformed when cells migrate

• allosteric activation when integrin binds to ligands allows the switching between active and inactive states by conf change of IC and EC domains

activation of integrins

OUTSIDE IN ACTIVATION

• binding of an extracellular ligand to an integrin results in binding to the cytoskeleton

• RGD amino acid sequence is recognised by the integrin

• this causes the alpha and beta subunits to mmove apart and frees up the tallin binding site which can bind tallin to the cytoskeleton

• transmission of force via cytoskeleton

INSIDE OUT ACTIVATION

• intracellular regulatory molecules such as phosphoinosotides activate tallin

• tallin binds to the beta integrin chain

• this causes teh extracellular domain of integrin to bind to extracellular ligands

• PIP2 is then produced in response to extracellular signals

selectin

• allows cells to roll across epithelium

• the cell surface carbohydrate binding proteins are called lectins

• single pass transmembrane protein

• heterophilic interactions —> binds oligosaccharides

• forms transient, weak interactions

• control of when and where selectins and integrins are expressed regulates movement of WBCs

• when the WBC reaches the site of injury, switches from selectin binding to integrin binding

• types of selectins

  • L selectin - WBCs

  • P selectin - platelets and endothelial cells

  • E selectin - activated endothelial cells

Ig superfamily CAMs

• mediate interactions between immune cells and endothelial lining

• contain immunoglobular like extracellular regions

• have a whole host of other functions depending on the type of CAM, such as barrier formation, cell signalling, synapse formation

EXAMPLE: NCAM

• stands for neursal cell adhesion molecule

• high levels of salicylic acid side chains which make them negatively charged which inhibits cell adhesion

• can be made more/less sticky depensing on post translational modifications

• NCAM has more subtle effects, more likely to be involves in the fine tuning of contacts

• NCAMs can drive the growth of axon to the cell body, when the axon reaches the cell body, contact is mediated by cadherins which anchor it down

cell attachment in plants

• pectin is important for cells to stick together

• breakdown of pectin causes the ripening of fruit

• Ca2+ presence and methylation state can affect how strong the pectin interaction is

• theres not just one type of pectin, there are many diff types

• pectin also has diff domains:

  1. homogalacturonan —> is the backbone of the pectin

  2. rhamnogalacturonan —> gives flexibility to the pectin

  3. xylogalacturonan —> forms cross links